Amarogentin incorporated in liposomes or niosomes may have clinical application in the treatment of leishmaniasis. It plays cemopreventive/therapeutic role during liver carcinogenesis through modulation of cell cycle and apoptosis. Amarogentin may offer therapeutic potential for preventing or treating thromboembolic disorders, it prevents platelet activation through the inhibition of PLC γ2-PKC cascade and MAPK pathway.
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Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months(2-8C)
Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.
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PLoS One. 2014 Mar 6;9(6):e90637.
The bitter barricading of prostaglandin biosynthesis pathway: understanding the molecular mechanism of selective cyclooxygenase-2 inhibition by amarogentin, a secoiridoid glycoside from Swertia chirayita.[Pubmed: 24603686
Amarogentin, a bitter secoiridoid glycoside from S. chirayita, shows varied activity in several patho-physiological conditions, predominantly in leishmaniasis and carcinogenesis. Experimental analysis has revealed that Amarogentin downregulates the cyclooxygenase-2 (COX-2) activity and helps to curtail skin carcinogenesis in mouse models; however, there exists no account on selective inhibition of the inducible cyclooxygenase (COX) isoform by Amarogentin.
METHODS AND RESULTS:
Hence the computer-aided drug discovery methods were used to unravel the COX-2 inhibitory mechanism of Amarogentin and to check its selectivity for the inducible isoform over the constitutive one. The generated theoretical models of both isoforms were subjected to molecular docking analysis with Amarogentin and twenty-one other Food and Drug Authority (FDA) approved lead molecules. The post-docking binding energy profile of Amarogentin was comparable to the binding energy profiles of the FDA approved selective COX-2 inhibitors. Subsequent molecular dynamics simulation analysis delineated the difference in the stability of both complexes, with Amarogentin-COX-2 complex being more stable after 40ns simulation. The total binding free energy calculated by MMGBSA for the Amarogentin-COX-2 complex was -52.35 KCal/mol against a binding free energy of -8.57 KCal/mol for Amarogentin-COX-1 complex, suggesting a possible selective inhibition of the COX-2 protein by the natural inhibitor. Amarogentin achieves this potential selectivity by small, yet significant, structural differences inherent to the binding cavities of the two isoforms. Hypothetically, it might block the entry of the natural substrates in the hydrophobic binding channel of the COX-2, inhibiting the cyclooxygenation step.
To sum up briefly, this work highlights the mechanism of the possible selective COX-2 inhibition by Amarogentin and endorses the possibility of obtaining efficient, futuristic and targeted therapeutic agents for relieving inflammation and malignancy from this phytochemical source.
J Antimicrob Chemother. 1999 Dec;44(6):791-4.
Evaluation of the in-vivo activity and toxicity of amarogentin, an antileishmanial agent, in both liposomal and niosomal forms.[Pubmed: 10590280
METHODS AND RESULTS:
The antileishmanial property of Amarogentin, a secoiridoid glycoside isolated from the Indian medicinal plant Swertia chirata, was examined in a hamster model of experimental leishmaniasis.
The therapeutic efficacy of Amarogentin was evaluated in free and two different vesicular forms, liposomes and niosomes. The Amarogentin in both liposomal and niosomal forms was found to be a more active leishmanicidal agent than the free Amarogentin; and the niosomal form was found to be more efficacious than the liposomal form at the same membrane microviscosity level. Toxicity studies involving blood pathology, histological staining of tissues and specific enzyme levels related to normal liver function showed no toxicity.
Hence, Amarogentin incorporated in liposomes or niosomes may have clinical application in the treatment of leishmaniasis.
Biomed Res Int. 2014;2014:728019.
Amarogentin, a secoiridoid glycoside, abrogates platelet activation through PLC γ 2-PKC and MAPK pathways.[Pubmed: 24868545
Amarogentin, an active principle of Gentiana lutea, possess antitumorigenic, antidiabetic, and antioxidative properties. Activation of platelets is associated with intravascular thrombosis and cardiovascular diseases.
METHODS AND RESULTS:
The present study examined the effects of Amarogentin on platelet activation. Amarogentin treatment (15~60 μM) inhibited platelet aggregation induced by collagen, but not thrombin, arachidonic acid, and U46619. Amarogentin inhibited collagen-induced phosphorylation of phospholipase C (PLC) γ2, protein kinase C (PKC), and mitogen-activated protein kinases (MAPKs). It also inhibits in vivo thrombus formation in mice. In addition, neither the guanylate cyclase inhibitor ODQ nor the adenylate cyclase inhibitor SQ22536 affected the Amarogentin-mediated inhibition of platelet aggregation, which suggests that Amarogentin does not regulate the levels of cyclic AMP and cyclic GMP.
In conclusion, Amarogentin prevents platelet activation through the inhibition of PLC γ2-PKC cascade and MAPK pathway. Our findings suggest that Amarogentin may offer therapeutic potential for preventing or treating thromboembolic disorders.
Carcinogenesis. 2012 Dec;33(12):2424-31.
Prevention of liver carcinogenesis by amarogentin through modulation of G1/S cell cycle check point and induction of apoptosis.[Pubmed: 22948180
Amarogentin, a secoiridoid glycoside, is an active component of the medicinal plant Swertia chirata.
METHODS AND RESULTS:
In this study, chemopreventive and chemotherapeutic actions of Amarogentin were evaluated in a carbon tetrachloride (CCl(4))/N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis mouse model system during continuous and posttreatment schedule. Better survival, no toxicity and increased body weight were noted in Amarogentin-treated mice. Reduction in proliferation and increase in apoptosis frequency were evident in Amarogentin-treated groups. In carcinogen control group moderate dysplasia, severe dysplasia and hepatocellular carcinoma were evident at 10th, 20th and 30th week, respectively. Amarogentin was found to prevent progression of liver carcinogenesis at mild dysplastic stage. Exposure to CCl(4)/NDEA resulted in upregulation of ppRb807/811, cyclinD1 and cdc25A at 10th week and additional activation of cMyc and mdm2 along with downregulation of LIMD1, p53 and p21 at 20th week. This was followed by activation of ppRb567 and downregulation of Rbsp3 at 30th week. Prevention of carcinogenesis by Amarogentin in both groups might be due to cumulative upregulation of LIMD1, RBSP3, p16 and downregulation of cdc25A at 10th week along with activation of p53 and p21 and downregulation of ppRb807/811 and ppRb567 at 20th week, followed by downregulation of cyclinD1, cMyc and mdm2 at 30th week. During carcinogenesis reduction of apoptosis was evident since 20th week. However, Amarogentin treatment could significantly induce apoptosis through upregulation of the Bax-Bcl2 ratio, activation of caspase-3 and poly ADP ribose polymerase cleavage.
This is the first report of chemopreventive/therapeutic role of Amarogentin during liver carcinogenesis through modulation of cell cycle and apoptosis.